DESCRIPTION: Work completed under the current award established that infectious disease as a cause of increased somnolence, and supported the hypothesis that sleep enhancement during microbial infections is related to the immune response. However, the precise interactions between sleep, infection and immunity remain largely undetermined. The fundamental goal of the proposed experiments is to discover the mechanisms responsible for sleep enhancement during infectious disease. Specific cytokines and cell populations are hypothesized to mediate sleep enhancement during microbial infections. This hypothesis will be tested by studying sleep in mice infected with influenza virus. Preliminary data suggest that endogenous somnogenic cytokines such as interferon play a role in mediating virus-induced sleep potentiation in mice. For example a strain of mice (C57BL/s) which possesses genes for high interferon production after viral infection shows marked sleep enhancement during influenza infection, whereas a strain (BALB/c) which possesses genes for low production does not. The proposed experiments will study mice with specific genetic or immunologically-induced impairments in immune function to determine which cellular mechanisms and endogenous somnogenic cytokines are associated with sleep during influenza infection. A related study will characterize the effects of microbial somnogens and somnogenic cytokines on neuronal firing patterns in brain regions that regulate sleep. These experiments will use rats implanted with microwire electrodes that permit repeated chronic recording from individual neurons.